ABSTRACT
BACKGROUND: Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time. OBJECTIVE: In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF. METHODS: The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test. RESULTS: The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 µm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability. CONCLUSION: The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.
ABSTRACT
The aim of this work was to study the effect of concomitant use of leucine and dipalmitoylphosphatidylcholine, in different ratios, on aerosolization performance of levodopa. Three-component formulations were selected based on a central composite design using percentages of leucine and dipalmitoylphosphatidylcholine as the independent variables. Particle size, surface roughness index, surface phosphorus and fine particle fraction were considered as dependent variables in the model. The spray dried samples were also characterized to determine their particle shape and solid state nature. levodopa was spray dried with 10-40% w/w of the excipients to prepare two- or three-component formulations. A crystalline nature was determined for levodopa in all samples spray dried from water:ethanol (30:70 v/v). Roughness in surface of the processed particles increased with increasing total concentration of the excipients, specially above 25% w/w. Analysis of phosphorus on the surface demonstrated that three-component formulations prepared with combination of 12.5% w/w leucine had the highest amount of dipalmitoylphosphatidylcholine in the surface, regardless of its percentage used in the initial feed. A combination of 12.43% w/w of leucine and 9.80% w/w of dipalmitoylphosphatidylcholine used in formulation exhibited the highest fine particle fraction (72.63%). It can be concluded that spray drying of levodopa with a suitable combination of both excipients leads to production of a three-component formulation of crystalline levodopa, with an aerosolization performance which is significantly higher than two-component formulations composed of the drug with either leucine or dipalmitoylphosphatidylcholine.
